tbuckley/cabot-search huggingface dataset:
Neurotoxicity and Outcomes from Developmental Lead Exposure: Persistent or Permanent?
Authors: Jay S. Schneider
Journal: Environmental Health Perspectives (2023)

Background: Childhood lead poisoning remains an important public health issue in the United States, as well as elsewhere in the world. Although primary prevention is a major goal and it is critically important to keep children from getting poisoned, it is also important to explore ways to reduce the neurotoxic effects of lead in those children already poisoned. Whether lead-induced neurotoxicity and its related adverse outcomes are viewed as "permanent" or "persistent" may influence the way in which potential remediation efforts are considered for improving outcomes from childhood lead poisoning. Objectives: The objective of this commentary was to discuss the ideas of permanence and persistence in relation to the direct neurotoxic effects of lead on the brain and the resulting adverse outcomes from these effects. Recent new insights regarding potential mitigation of lead-induced neurotoxic effects on brain and behavior are considered along with clinical information on neurorehabilitation to suggest potential strategies for improving cognitive/behavioral outcomes in lead-poisoned children. Discussion: The distinction between permanent and persistent in regard to lead-induced neurotoxicity and its resulting outcomes may have broad implications for public health policies in response to the problem of childhood lead exposure. The term permanent implies that the damage is irreversible with little chance of improvement. However, there is evidence that at least some of the adverse cognitive/behavioral outcomes from lead exposure are persistent rather than permanent and potentially amenable, under the appropriate circumstances, to some level of mitigation. This author recommends that clinical, interventional research efforts be devoted to exploring optimal neurorehabilitative and enrichment conditions to stimulate plasticity and enhance functioning to determine the extent to which promising results from preclinical studies of lead-induced brain damage and the mitigation of these effects can be successfully translated to humans. https://doi.org/10.1289/EHP12371
Opportunities and challenges for microbiomics in ecosystem restoration
Authors: Jake M. Robinson, Riley Hodgson, Siegfried L. Krauss, Craig Liddicoat, Ashish A. Malik, Belinda C. Martin, Jakki J. Mohr, David Moreno-Mateos, Miriam Muñoz-Rojas, Shawn D. Peddle, Martin F. Breed
Journal: Trends in Ecology & Evolution (2023)
The Neurological Pupil index for outcome prognostication in people with acute brain injury (ORANGE): a prospective, observational, multicentre cohort study
Authors: Mauro Oddo, Fabio S Taccone, Matteo Petrosino, Rafael Badenes, Aaron Blandino-Ortiz, Pierre Bouzat, Anselmo Caricato, Randall M Chesnut, Anders C Feyling, Nawfel Ben-Hamouda, J Claude Hemphill, Julia Koehn, Frank Rasulo, Jose I Suarez, Francesca Elli, Alessia Vargiolu, Paola Rebora, Stefania Galimberti, Giuseppe Citerio, Samia Abed-Maillard, Marco Anderloni, Alessandra Beretta, Sung-Min Cho, Silvia Del Bianco, Eva Favre, Madeline E. Greil, Angelo Guglielmi, Juan Higuera Lucas, Cosimo Iacca, Joji B. Kuramatsu, Linda Marie Lundberg, Federico Magni, Letterio Malgeri, Paolo Mangili, Isabella Melchionda, John-Paul Miroz, Berta Monleón, Dominica Randazzo, Samia Salah, Angela Scavone, Clothilde Schilte, Serena Silva, Kjetil Sunde, Ruihao Wang
Journal: The Lancet Neurology (2023)
From private incentives to public health need: rethinking research and development for pandemic preparedness
Authors: Els Torreele, Daniel Wolfe, Michel Kazatchkine, Amadou Sall, Kiat Ruxrungtham, Joseph Robert Anderson Fitchett, Joanne Liu, Gary Kobinger, Claudia Vaca-González, Carolina Gómez, Petro Terblanche, Soumya Swaminathan, Piero Olliaro, Helen Clark
Journal: The Lancet Global Health (2023)

Pandemic preparedness and response have relied primarily on market dynamics to drive development and availability of new health products. Building on calls for transformation, we propose a new value proposition that instead prioritises equity from the research and development (R&D) stage and that strengthens capacity to control outbreaks when and where they occur. Key elements include regional R&D hubs free to adapt well established technology platforms, and independent clinical trials networks working with researchers, regulators, and health authorities to better study questions of comparative benefit and real-world efficacy. Realising these changes requires a shift in emphasis: from pandemic response to outbreak control, from one-size-fits-all economies of scale to R&D and manufacture for local need, from de novo product development to last-mile innovation through adaptation of existing technologies, and from proprietary, competitive R&D to open science and financing for the common good that supports collective management and sharing of technology and know-how.
Respiratory management and outcomes in high-risk preterm infants with development of a population outcome dashboard
Authors: Tng Chang Kwok, Caroline Poulter, Saleh Algarni, Lisa Szatkowski, Don Sharkey
Journal: Thorax (2023)

Introduction Bronchopulmonary dysplasia (BPD) is associated with adverse long-term respiratory and neurodevelopmental outcomes. No recent studies examined the changing respiratory management and outcomes, particularly severe BPD, across a whole population. Purpose Evaluate the temporal trends in the respiratory management and outcomes of preterm infants born below 32 weeks gestational age and develop an individualised dashboard of the incidence of neonatal outcome. Methods Using the National Neonatal Research Database, we determined changes in respiratory management, BPD rates, postdischarge respiratory support and mortality in 83 463 preterm infants in England and Wales from 2010 to 2020. Results Between 2010 and 2020, antenatal corticosteroids use increased (88%–93%, p&lt;0.0001) and neonatal surfactant use decreased (65%–60%, p&lt;0.0001). Postnatal corticosteroid use increased, especially dexamethasone (4%–6%, p&lt;0.0001). More recently, hydrocortisone and budesonide use increased from 2% in 2017 to 4% and 3%, respectively, in 2020 (p&lt;0.0001). Over the study period, mortality decreased (10.1%–8.5%), with increases in BPD (28%–33%), severe BPD (12%–17%), composite BPD/death (35%–39%) and composite severe BPD/death (21%–24%) (all p&lt;0.0001). Overall, 11 684 infants required postdischarge respiratory support, increasing from 13% to 17% (p&lt;0.0001), with 1843 infants requiring respiratory pressure support at discharge. A population dashboard ( https://premoutcome.github.io/ ) depicting the incidence of mortality and respiratory outcomes, based on gestation, sex and birthweight centile, was developed. Conclusion More preterm infants are surviving with worse respiratory outcomes, particularly severe BPD requiring postdischarge respiratory support. Ultimately, these survivors will develop chronic respiratory diseases requiring greater healthcare resources.
Risk of Nephrolithiasis in Adults Heterozygous for SLC34A3 Ser192Leu in an Unselected Health System Cohort
Authors: Chinedu Nwachukwu, Gurmukteshwar Singh, Bryn Moore, Natasha T. Strande, Ion D. Bucaloiu, Alexander R. Chang
Journal: Journal of the American Society of Nephrology (2023)

Nwachukwu, Chinedu; Singh, Gurmukteshwar; Moore, Bryn; Strande, Natasha T.; Bucaloiu, Ion D.; Chang, Alexander R. Author Information
Unified Mouse and Human Kidney Single-Cell Expression Atlas Reveal Commonalities and Differences in Disease States
Authors: Jianfu Zhou, Amin Abedini, Michael S. Balzer, Rojesh Shrestha, Poonam Dhillon, Hongbo Liu, Hailong Hu, Katalin Susztak
Journal: Journal of the American Society of Nephrology (2023)

Mouse models have been widely used to understand kidney disease pathomechanisms and play an important role in drug discovery. However, these models have not been systematically analyzed and compared. The authors characterized 18 different mouse kidney disease models at both bulk and single-cell gene expression levels and compared single-cell gene expression data from diabetic kidney disease (DKD) mice and from patients with DKD. Although single cell-level gene expression changes were mostly model-specific, different disease models showed similar changes when compared at a pathway level. The authors also found that changes in fractions of cell types are major drivers of bulk gene expression differences. Although the authors found only a small overlap of single cell-level gene expression changes between the mouse DKD model and patients, they observed consistent pathway-level changes.
Pay-it-forward incentives for hepatitis virus testing in men who have sex with men: a cluster randomized trial
Authors: Ye Zhang, Jianjun Li, Yewei Xie, Dan Wu, Jason Ong, Gifty Marley, Adeeba Kamarulzaman, Haidong Lu, Fei Zou, Jennifer S. Smith, Joseph D. Tucker, Gengfeng Fu, Weiming Tang
Journal: Nature Medicine (2023)
Cell-free DNA methylome analysis for early preeclampsia prediction
Authors: Marie De Borre, Huiwen Che, Qian Yu, Lore Lannoo, Kobe De Ridder, Leen Vancoillie, Pauline Dreesen, Mika Van Den Ackerveken, Mio Aerden, Eva Galle, Jeroen Breckpot, Joachim Van Keirsbilck, Wilfried Gyselaers, Koen Devriendt, Joris Robert Vermeesch, Kristel Van Calsteren, Bernard Thienpont
Journal: Nature Medicine (2023)
Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial
Authors: Angela R. Branche, Nadine G. Rouphael, David J. Diemert, Ann R. Falsey, Cecilia Losada, Lindsey R. Baden, Sharon E. Frey, Jennifer A. Whitaker, Susan J. Little, Evan J. Anderson, Emmanuel B. Walter, Richard M. Novak, Richard Rupp, Lisa A. Jackson, Tara M. Babu, Angelica C. Kottkamp, Anne F. Luetkemeyer, Lilly C. Immergluck, Rachel M. Presti, Martín Bäcker, Patricia L. Winokur, Siham M. Mahgoub, Paul A. Goepfert, Dahlene N. Fusco, Elissa Malkin, Jeffrey M. Bethony, Edward E. Walsh, Daniel S. Graciaa, Hady Samaha, Amy C. Sherman, Stephen R. Walsh, Getahun Abate, Zacharoula Oikonomopoulou, Hana M. El Sahly, Thomas C. S. Martin, Satoshi Kamidani, Michael J. Smith, Benjamin G. Ladner, Laura Porterfield, Maya Dunstan, Anna Wald, Tamia Davis, Robert L. Atmar, Mark J. Mulligan, Kirsten E. Lyke, Christine M. Posavad, Megan A. Meagher, David S. Stephens, Kathleen M. Neuzil, Kuleni Abebe, Heather Hill, Jim Albert, Kalyani Telu, Jinjian Mu, Teri C. Lewis, Lisa A. Giebeig, Amanda Eaton, Antonia Netzl, Samuel H. Wilks, Sina Türeli, Mamodikoe Makhene, Sonja Crandon, David C. Montefiori, Mat Makowski, Derek J. Smith, Seema U. Nayak, Paul C. Roberts, John H. Beigel, Edward Walsh, Patrick Kingsley, Kari Steinmetz, Michael Peasley, Cassie Grimsley Ackerley, Kristen E. Unterberger, Aimee Desrosiers, Marc Siegel, Alexandra Tong, Rebecca Rooks, Daniel F. Hoft, Irene Graham, Wendy A. Keitel, C. Mary Healy, Nicole Carter, Steven Hendrickx, Christina A. Rostad, Etza Peters, Lauren Nolan, M. Anthony Moody, Kenneth E. Schmader, Andrea Wendrow, Jessica Herrick, Rebecca Lau, Barbara Carste, Taylor Krause, Kirsten Hauge, Celia Engelson, Vijaya Soma, Chloe Harris, Azquena Munoz Lopez, Erica Johnson, Austin Chan, Fatima Ali, Trisha Parker, Jane A. O’Halloran, Ryley M. Thompson, Kimberly Byrnes, Asif Noor, Jeffery Meier, Jack Stapleton, Celia Maxwell, Sarah Shami, Arnaud C. Drouin, Florice K. Numbi, Julie McElrath, Mike Gale, Holly Baughman, Lisa McQuarrie, Theresa M. Engel, Caleb J. Griffith, Wendi L. McDonald, Alissa E. Burkey, Lisa B. Hoopengardner, Jessica E. Linton, Nikki L. Gettinger, Marina Lee, Mohamed Elsafy, Rhonda Pikaart-Tautges, Janice Arega, Binh Hoang, None Dan Curtin, Hyung Koo, Elisa Sindall, Marciela M. DeGrace, Diane J. Post, David S. Stephens, Kathleen M. Neuzil, Monica M. Farley, Jeanne Marrazzo, Sidnee Paschal Young, Jeffery Lennox, Robert L. Atmar, Linda McNeil, Elizabeth Brown
Journal: Nature Medicine (2023)

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID
The role of recruitment versus training in influenza-induced lasting changes to alveolar macrophage function
Authors: Chrysante S. Iliakis, Justina Kulikauskaite, Helena Aegerter, Fengqi Li, Federica Piattini, Claudia V. Jakubzick, Martin Guilliams, Manfred Kopf, Andreas Wack
Journal: Nature Immunology (2023)
Solanum americanum genome-assisted discovery of immune receptors that detect potato late blight pathogen effectors
Authors: Xiao Lin, Yuxin Jia, Robert Heal, Maxim Prokchorchik, Maria Sindalovskaya, Andrea Olave-Achury, Moffat Makechemu, Sebastian Fairhead, Azka Noureen, Jung Heo, Kamil Witek, Matthew Smoker, Jodie Taylor, Ram-Krishna Shrestha, Yoonyoung Lee, Chunzhi Zhang, Soon Ju Park, Kee Hoon Sohn, Sanwen Huang, Jonathan D. G. Jones
Journal: Nature Genetics (2023)

Abstract Potato ( Solanum tuberosum ) and tomato ( Solanum lycopersicon ) crops suffer severe losses to late blight caused by the oomycete pathogen Phytophthora infestans . Solanum americanum , a relative of potato and tomato, is globally distributed and most accessions are highly blight resistant. We generated high-quality reference genomes of four S. americanum accessions, resequenced 52 accessions, and defined a pan-NLRome of S. americanum immune receptor genes. We further screened for variation in recognition of 315 P. infestans RXLR effectors in 52 S. americanum accessions. Using these genomic and phenotypic data, we cloned three NLR-encoding genes, Rpi-amr4 , R02860 and R04373 , that recognize cognate P. infestans RXLR effectors PITG_22825 ( AVRamr4 ), PITG_02860 and PITG_04373 . These genomic resources and methodologies will support efforts to engineer potatoes with durable late blight resistance and can be applied to diseases of other crops.
Cell cycle-linked vacuolar pH dynamics regulate amino acid homeostasis and cell growth
Authors: Voytek Okreglak, Rachel Ling, Maria Ingaramo, Nathaniel H. Thayer, Alfred Millett-Sikking, Daniel E. Gottschling
Journal: Nature Metabolism (2023)

Abstract Amino acid homeostasis is critical for many cellular processes. It is well established that amino acids are compartmentalized using pH gradients generated between organelles and the cytoplasm; however, the dynamics of this partitioning has not been explored. Here we develop a highly sensitive pH reporter and find that the major amino acid storage compartment in Saccharomyces cerevisiae , the lysosome-like vacuole, alkalinizes before cell division and re-acidifies as cells divide. The vacuolar pH dynamics require the uptake of extracellular amino acids and activity of TORC1, the v-ATPase and the cycling of the vacuolar specific lipid phosphatidylinositol 3,5-bisphosphate, which is regulated by the cyclin-dependent kinase Pho85 (CDK5 in mammals). Vacuolar pH regulation enables amino acid sequestration and mobilization from the organelle, which is important for mitochondrial function, ribosome homeostasis and cell size control. Collectively, our data provide a new paradigm for the use of dynamic pH-dependent amino acid compartmentalization during cell growth/division.
A machine learning classifier using 33 host immune response mRNAs accurately distinguishes viral and non-viral acute respiratory illnesses in nasal swab samples
Authors: Rushika Pandya, Yudong D. He, Timothy E. Sweeney, Yehudit Hasin-Brumshtein, Purvesh Khatri
Journal: Genome Medicine (2023)

Viral acute respiratory illnesses (viral ARIs) contribute significantly to human morbidity and mortality worldwide, but their successful treatment requires timely diagnosis of viral etiology, which is complicated by overlap in clinical presentation with the non-viral ARIs. Multiple pandemics in the twenty-first century to date have further highlighted the unmet need for effective monitoring of clinically relevant emerging viruses. Recent studies have identified conserved host response to viral infections in the blood.We hypothesize that a similarly conserved host response in nasal samples can be utilized for diagnosis and to rule out viral infection in symptomatic patients when current diagnostic tests are negative. Using a multi-cohort analysis framework, we analyzed 1555 nasal samples across 10 independent cohorts dividing them into training and validation.Using six of the datasets for training, we identified 119 genes that are consistently differentially expressed in viral ARI patients (N = 236) compared to healthy controls (N = 146) and further down-selected 33 genes for classifier development. The resulting locked logistic regression-based classifier using the 33-mRNAs had AUC of 0.94 and 0.89 in the six training and four validation datasets, respectively. Furthermore, we found that although trained on healthy controls only, in the four validation datasets, the 33-mRNA classifier distinguished viral ARI from both healthy or non-viral ARI samples with > 80% specificity and sensitivity, irrespective of age, viral type, and viral load. Single-cell RNA-sequencing data showed that the 33-mRNA signature is dominated by macrophages and neutrophils in nasal samples.This proof-of-concept signature has potential to be adapted as a clinical point-of-care test ('RespVerity') to improve the diagnosis of viral ARIs.
A high-resolution genotype–phenotype map identifies the TaSPL17 controlling grain number and size in wheat
Authors: Yangyang Liu, Jun Chen, Changbin Yin, Ziying Wang, He Wu, Kuocheng Shen, Zhiliang Zhang, Lipeng Kang, Song Xu, Aoyue Bi, Xuebo Zhao, Daxing Xu, Zhonghu He, Xueyong Zhang, Chenyang Hao, Jianhui Wu, Yan Gong, Xuchang Yu, Zhiwen Sun, Botao Ye, Danni Liu, Lili Zhang, Liping Shen, Yuanfeng Hao, Youzhi Ma, Fei Lu, Zifeng Guo
Journal: Genome biology (2023)

Large-scale genotype-phenotype association studies of crop germplasm are important for identifying alleles associated with favorable traits. The limited number of single-nucleotide polymorphisms (SNPs) in most wheat genome-wide association studies (GWASs) restricts their power to detect marker-trait associations. Additionally, only a few genes regulating grain number per spikelet have been reported due to sensitivity of this trait to variable environments.We perform a large-scale GWAS using approximately 40 million filtered SNPs for 27 spike morphology traits. We detect 132,086 significant marker-trait associations and the associated SNP markers are located within 590 associated peaks. We detect additional and stronger peaks by dividing spike morphology into sub-traits relative to GWAS results of spike morphology traits. We propose that the genetic dissection of spike morphology is a powerful strategy to detect signals for grain yield traits in wheat. The GWAS results reveal that TaSPL17 positively controls grain size and number by regulating spikelet and floret meristem development, which in turn leads to enhanced grain yield per plant. The haplotypes at TaSPL17 indicate geographical differentiation, domestication effects, and breeding selection.Our study provides valuable resources for genetic improvement of spike morphology and a fast-forward genetic solution for candidate gene detection and cloning in wheat.
Ariadne: synthetic long read deconvolution using assembly graphs
Authors: Lauren Mak, Dmitry Meleshko, David C. Danko, Waris N. Barakzai, Salil Maharjan, Natan Belchikov, Iman Hajirasouliha
Journal: Genome biology (2023)

Synthetic long read sequencing techniques such as UST's TELL-Seq and Loop Genomics' LoopSeq combine 3[Formula: see text] barcoding with standard short-read sequencing to expand the range of linkage resolution from hundreds to tens of thousands of base-pairs. However, the lack of a 1:1 correspondence between a long fragment and a 3[Formula: see text] unique molecular identifier confounds the assignment of linkage between short reads. We introduce Ariadne, a novel assembly graph-based synthetic long read deconvolution algorithm, that can be used to extract single-species read-clouds from synthetic long read datasets to improve the taxonomic classification and de novo assembly of complex populations, such as metagenomes.
Different levels of healing in inflammatory bowel diseases: mucosal, histological, transmural, barrier and complete healing
Authors: Markus F Neurath, Michael Vieth
Journal: Gut (2023)

Mucosal healing on endoscopy has emerged as a key prognostic parameter in the management of patients with IBD (Crohn's disease, ulcerative colitis/UC) and can predict sustained clinical remission and resection-free survival. The structural basis for this type of mucosal healing is a progressive resolution of intestinal inflammation with associated healing of ulcers and improved epithelial barrier function. However, in some cases with mucosal healing on endoscopy, evidence of histological activity in mucosal biopsies has been observed. Subsequently, in UC, a second, deeper type of mucosal healing, denoted histological healing, was defined which requires the absence of active inflammation in mucosal biopsies. Both levels of mucosal healing should be considered as initial events in the resolution of gut inflammation in IBD rather than as indicators of complete transmural healing. In this review, the effects of anti-inflammatory, biological or immunosuppressive agents as well as small molecules on mucosal healing in clinical studies are highlighted. In addition, we focus on the implications of mucosal healing for clinical management of patients with IBD. Moreover, emerging techniques for the analysis of mucosal healing as well as potentially deeper levels of mucosal healing such as transmural healing and functional barrier healing of the mucosa are discussed. Although none of these new levels of healing indicate a definitive cure of the diseases, they make an important contribution to the assessment of patients' prognosis. The ultimate level of healing in IBD would be a resolution of all aspects of intestinal and extraintestinal inflammation (complete healing).
Recent advances in targeted strategies for triple-negative breast cancer
Authors: Shuangli Zhu, Yuze Wu, Bin Song, Ming Yi, Yuheng Yan, Qi Mei, Kongming Wu
Journal: Journal of Hematology & Oncology (2023)

Triple-negative breast cancer (TNBC), a highly aggressive subtype of breast cancer, negatively expresses estrogen receptor, progesterone receptor, and the human epidermal growth factor receptor 2 (HER2). Although chemotherapy is the main form of treatment for patients with TNBC, the effectiveness of chemotherapy for TNBC is still limited. The search for more effective therapies is urgent. Multiple targeted therapeutic strategies have emerged according to the specific molecules and signaling pathways expressed in TNBC. These include PI3K/AKT/mTOR inhibitors, epidermal growth factor receptor inhibitors, Notch inhibitors, poly ADP-ribose polymerase inhibitors, and antibody-drug conjugates. Moreover, immune checkpoint inhibitors, for example, pembrolizumab, atezolizumab, and durvalumab, are widely explored in the clinic. We summarize recent advances in targeted therapy and immunotherapy in TNBC, with the aim of serving as a reference for the development of individualized treatment of patients with TNBC in the future.
miR-126 identifies a quiescent and chemo-resistant human B-ALL cell subset that correlates with minimal residual disease
Authors: Carolina Caserta, Silvia Nucera, Matteo Barcella, Grazia Fazio, Matteo Maria Naldini, Riccardo Pagani, Francesca Pavesi, Giacomo Desantis, Erika Zonari, Mariella D’Angiò, Paola Capasso, Angelo Lombardo, Ivan Merelli, Orietta Spinelli, Alessandro Rambaldi, Fabio Ciceri, Daniela Silvestri, Maria Grazia Valsecchi, Andrea Biondi, Giovanni Cazzaniga, Bernhard Gentner
Journal: Leukemia (2023)